During the past several years it has become increasingly apparent that the apolipoprotein composition of the majority of plasma lipoproteins is governed by the laws of mass action. Moreover, the rate constants are such that many, if not the majority, of apolipoproteins exist in a dynamic equilibrium between plasma lipoproteins. Thus, the distribution of most apolipoproteins in plasma is governed by their affinity for, and the relative concentration of, plasma lipoproteins. This work is directed towards a greater understanding of the molecular forces involved in these interactions between plasma lipoproteins. The first phase of this investigation is necessarily a quantitative evaluation of the molecular properties of apolipoproteins in aqueous solution. Apolipoproteins A-I, AII, and C-I each self-associate in aqueous solution with major changes in secondary, tertiary and of course quaternary structure. Apolipoprotein C-III also self-associates, but in contrast to the apolipoproteins discussed above, undergoes very little change in secondary and tertiary structure with association. These studies have formed a framework for the quantitative evaluation of apolipoprotein-apolipoprotein and apolipoprotein-plasma lipoprotein interactions in plasma.